Cystic fibrosis (CF) is a highly morbid, autosomal recessive disease caused by one or more mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The CFTR protein is important in transporting sodium and chloride ions through the membranes of epithelial cells lining the lungs and other organs. In Caucasians, CF is the most lethal inherited disease of childhood (frequency of 1:3,300). In the U.S., about 25,000 people have CF and about 850 individuals are diagnosed with CF each year. CF affects all races and ethnic groups and it is underdiagnosed, especially in minorities. Present genetic screening assays are best suited for detecting CF in Caucasians and Ashkenazi Jews but, the mutations currently assayed for in the CF screening does not detect mutations specific for Black Americans and Hispanics. Electronic microtransponders will be used in a novel DNA detection system to quickly and accurately detect large numbers of CF DNA mutations in a single high-speed flow assay. Each microtransponder is an integrated circuit composed of photocells, memory and antenna. It stores information identifying the sequence of an attached oligonucleotide probe in its electronic memory. Complementary, dye-tagged target DNA sequences bind to probes on microtransponders and the results are read in a high-speed flow reader. The Specific Aims of Phase I are to prove feasibility of a novel, rapid and inexpensive microtransponder-based CFTR screening assay: 1) Select ten important cystic fibrosis (CF) mutations in Caucasians, Black Americans and Hispanics and prepare synthetic DNA probes to these mutations; 2) Prepare primers for all CFTR mutations tested for use in multiplex PCR reaction; 3) Covalently attach optimized DNA probes to microtransponders, perform a microtransponder-based DNA probe assay using cell lines containing CFTR gene mutations and match results to purchased cell line descriptions; 4) Perform the microtransponder CF assay on a small number of patient and control samples and compare results to standard methods used in a genetics laboratory in a major medical center in New Jersey. The microtransponder-based, multiplex assay proposed with extended mutation detection for domestic ethnic groups will significantly increase the utility of this important assay for more U.S. patients by adding important CFTR mutations observed in Blacks and Hispanics into a single, affordable, accurate, high-speed assay.